DESCRIPTION: (Adapted from the applicants abstract) Previous studies by the investigator suggest that muscle catabolism seen during sepsis is the result of protein breakdown, specifically in myofibrillar protein. Glucocorticoids, tumor necrosis factor (TNF), and interleukin-1 (IL-1) mediate some of these metabolic changes. The proposed studies are designed to test the following hypotheses: 1) sepsis upregulates the activity and expression of the 20S proteosome in the energy dependent ubiquitin proteolytic pathway, 2) the ubiquitin pathway is regulated in part by glucocorticoids and/or cytokines, 3) muscle catabolism in sepsis reflects stimulated ubiquitin activity. They will use a cecal ligation and puncture model with sham operated animals as controls. Total and myofibrillar protein breakdown will be measured in incubated muscles. Muscle levels of ubiqutin and ubiquitin message will be determined by northern and western blotting techniques. This group also plans to characterize mRNA expression in sepsis by the differential display technique. The ultimate goal of the project is to gain further insight into the exact mechanisms of sepsis-induced muscle catabolism with elucidation of the specific roles of glucocorticoids and cytokines.